The benefits of this treatment combo outweigh the increased risk for akathisia -- agitation and restlessness -- and Parkinsonism, a condition similar to Parkinson's disease, the researchers say.

"Doctors and patients should not settle for a partial response from antidepressant treatment," says lead researcher Eric Lenze, MD, a professor of psychiatry at Washington University School of Medicine in St Louis. "We need to use (additional) treatments in order to help patients get well from depression."

The study was published online this week.

Lots of older adults with major depression don't get relief from standard treatments -- a problem that doctors call treatment resistance.

But doctors have little guidance on using additional treatments besides antidepressant medications for these patients, according to Lenze.

Research Details

The study included over 460 participants in the U.S. and Canada who took the extended-release version of venlafaxine.

Of them, 181 had treatment-resistant depression, which the researchers defined as not getting relief after at least 12 weeks of treatment, with 4 weeks or longer at the highest tolerated dose.

The researchers randomly chose 91 of them to start taking the antipsychotic drug aripiprazole with their depression treatment. The other 90 began taking a placebo pill with their antidepressant.

Researchers chose aripiprazole as the additional drug in the study in part because it doesn't make people feel sleepy, Lenze says. It's also used for schizophrenia, bipolar disorder, and autism. The FDA approved it in 2007 as an add-on treatment for major depressive disorder.

Forty-four percent of the participants taking aripiprazole with their antidepressant got some relief from their depression, compared with 29% of those taking a placebo.

But compared to the patients who took a placebo pill, more people taking the antipsychotic developed akathisia (26%, vs 12%) and Parkinsonism (17% vs 2%). But the akathisia was typically mild and temporary, Lenze says.

More people in the treatment group reported weight gain (20% vs. 9%) compared with those in the placebo group. Lenze says the weight gain could be concerning. But he pointed out that people in the treatment group did not gain more total body fat than the patients taking placebo.

Clinically Important

The researchers did a number of things "really well," says Brent P. Forester, MD, chief of the Division of Geriatric Psychiatry at Mclean Hospital.

These included treating all participants with the same antidepressant and comparing the group receiving placebo with the treatment group for 12 weeks, "which is a good amount of time."

Although there have been several studies of depression in older adults, these generally involved a single medication in comparison with placebo and lasted fewer than 12 weeks, Forester says.

A remission rate of 44% for treatment vs. 29% for placebo in the study is an important finding, he says.

Forester says there were no very old people in the study.

He pointed out that some people, such as those with other medical problems or anxiety, which is common in older adults with depression, respond less well to an antipsychotic. "It would be interesting to see if this combination would be effective and safe in an older population with depression and mild dementia," Forester says.

The FDA has a black box warning about a higher rate of death and stroke when using an antipsychotic to treat people with dementia along with psychosis and agitation. The current study excluded people with dementia.

Dr. Lenze has received research support from the National Institute of Mental Health, the National Institute on Aging, the National Center for Complementary and Integrative Health, Roche, Lundbeck, the Sidney R. Baer Foundation, the Taylor Family Institute for Innovative Psychiatric Research, the Barnes-Jewish Foundation, and the McKnight Brain Research Foundation.